The long term objective of this study is to identify a synthetic derivative of the iron-complexing agent deferoxamine which is effective when administered orally. Because of low oral bioavailability (< 15 %), deferoxamine is currently available for injection only. Preliminary studies have resulted in the hypothesis that deferoxamine absorption is limited because: l) it is unstable in the acidic environment of the stomach; and 2) the very low partition coefficient and ionized amine group restrict passive absorption. Therefore, we proposed that bonding lipophilic side- chains to the primary amino group would eliminate these properties and enhance membrane permeability. A total of eleven derivatives have been synthesized and their aqueous solubilities and partition coefficients determined. Each derivative should complex iron to a similar extent to deferoxamine as well as function a prodrug for deferoxamine. The specific aims of this research are: 1) to complete the physicochemical characterization of these derivatives i.e., determine iron complexation constants, ionization constants, diffusional flux and stability in plasma; and 2) to compare the oral bioavailability of these derivatives, selected based on their absorption potentials, to that of deferoxamine. Standard experimental procedures will be used to determine the physicochemical properties identified in specific aim 1, while oral biovailability will be evaluated using rats. Deferoxamine is the only FDA approved chelating agent for the treatment of acute or chronic iron toxicity. interest in deferoxamine is growing as more recently it has been reported that the drug may be useful in the treatment of other diseases such as Alzheimer's disease, some forms of malaria and cancer. A derivative of this deferoxamine which is absorbed across gastrointestinal membranes, and sustains therapeutic plasma levels should increase efficacy and greatly reduce hospitalization costs for patients requiring deferoxamine.